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Relationship Between the Lipidome Profile and Disease Activity in Patients with Rheumatoid Arthritis

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Abstract

Lipid mediators have been suggested to play important roles in the pathogenesis of rheumatoid arthritis (RA). Lipidomics has recently allowed for the comprehensive analysis of lipids and has revealed the potential of lipids as biomarkers for the early diagnosis of RA and prediction of therapeutic responses. However, the relationship between disease activity and the lipid profile in RA remains unclear. In the present study, we performed a plasma lipidomic analysis of 278 patients with RA during treatment and examined relationships with disease activity using the Disease Activity Score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR). In all patients, five lipids positively correlated and seven lipids negatively correlated with DAS28-ESR. Stearic acid [FA(18:0)] (r = -0.45) and palmitic acid [FA(16:0)] (r = -0.38) showed strong negative correlations. After adjustments for age, body mass index (BMI), and medications, stearic acid, palmitic acid, bilirubin, and lysophosphatidylcholines negatively correlated with disease activity. Stearic acid inhibited osteoclast differentiation from peripheral blood monocytes in in vitro experiments, suggesting its contribution to RA disease activity by affecting bone metabolism. These results indicate that the lipid profile correlates with the disease activity of RA and also that some lipids may be involved in the pathogenesis of RA.

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Data Availability

The datasets generated or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. McInnes, I.B., and G. Schett. 2011. The pathogenesis of rheumatoid arthritis. New England Journal of Medicine 365: 2205–2219.

    Article  CAS  PubMed  Google Scholar 

  2. Xue, J., L. Xu, H. Zhu, M. Bai, X. Li, Z. Zhao, H. Zhong, G. Cheng, X. Li, F. Hu, et al. 2020. CD14(+)CD16(-) monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK. Arthritis Research & Therapy 22: 221.

    Article  CAS  Google Scholar 

  3. Gengenbacher, M., H.J. Sebald, P.M. Villiger, W. Hofstetter, and M. Seitz. 2008. Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with rheumatoid arthritis and ankylosing spondylitis. Annals of the Rheumatic Diseases 67: 620–624.

    Article  CAS  PubMed  Google Scholar 

  4. Shang, W., L.J. Zhao, X.L. Dong, Z.M. Zhao, J. Li, B.B. Zhang, and H. Cai. 2016. Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways. Molecular Medicine Reports 14: 3620–3626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Leuti, A., D. Fazio, M. Fava, A. Piccoli, S. Oddi, and M. Maccarrone. 2020. Bioactive lipids, inflammation and chronic diseases. Advanced Drug Delivery Reviews 159: 133–169.

    Article  CAS  PubMed  Google Scholar 

  6. Dorochow, E., M. Kohm, L. Hahnefeld, and R. Gurke. 2022. Metabolic profiling in rheumatoid arthritis, psoriatic arthritis, and psoriasis: Elucidating pathogenesis, improving diagnosis, and monitoring disease activity. Journal of Personalized Medicine 12: 924.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Luczaj, W., A. Moniuszko-Malinowska, P. Domingues, M.R. Domingues, E. Gindzienska-Sieskiewicz, and E. Skrzydlewska. 2018. Plasma lipidomic profile signature of rheumatoid arthritis versus Lyme arthritis patients. Archives of Biochemistry and Biophysics 654: 105–114.

    Article  CAS  PubMed  Google Scholar 

  8. Cuppen, B.V., J. Fu, H.A. van Wietmarschen, A.C. Harms, S. Koval, A.C. Marijnissen, J.J. Peeters, J.W. Bijlsma, J. Tekstra, J.M. van Laar, et al. 2016. Exploring the Inflammatory Metabolomic Profile to Predict Response to TNF-alpha Inhibitors in Rheumatoid Arthritis. PLoS ONE 11: e0163087.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Luan, H., W. Gu, H. Li, Z. Wang, L. Lu, M. Ke, J. Lu, W. Chen, Z. Lan, Y. Xiao, et al. 2021. Serum metabolomic and lipidomic profiling identifies diagnostic biomarkers for seropositive and seronegative rheumatoid arthritis patients. Journal of Translational Medicine 19: 500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Koh, J.H., S.J. Yoon, M. Kim, S. Cho, J. Lim, Y. Park, H.S. Kim, S.W. Kwon, and W.U. Kim. 2022. Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis. Experimental & Molecular Medicine 54: 143–155.

    Article  CAS  Google Scholar 

  11. Aletaha, D., T. Neogi, A.J. Silman, J. Funovits, D.T. Felson, C.O. Bingham 3rd., N.S. Birnbaum, G.R. Burmester, V.P. Bykerk, M.D. Cohen, et al. 2010. 2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Annals of the Rheumatic Diseases 69: 1580–1588.

    Article  PubMed  Google Scholar 

  12. Saito, K., Y. Ohno, and Y. Saito. 2017. Enrichment of resolving power improves ion-peak quantification on a lipidomics platform. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 1055–1056: 20–28.

    Article  PubMed  Google Scholar 

  13. Saito, K., M. Ikeda, Y. Kojima, H. Hosoi, Y. Saito, and S. Kondo. 2018. Lipid profiling of pre-treatment plasma reveals biomarker candidates associated with response rates and hand-foot skin reactions in sorafenib-treated patients. Cancer Chemotherapy and Pharmacology 82: 677–684.

    Article  CAS  PubMed  Google Scholar 

  14. Prevoo, M.L., M.A. van’t Hof, H.H. Kuper, M.A. van Leeuwen, L.B. van de Putte, and P.L. van Riel. 1995. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis & Rheumatism 38: 44–48.

    Article  CAS  Google Scholar 

  15. Rodriguez-Carrio, J., M. Alperi-Lopez, P. Lopez, F.J. Ballina-Garcia, and A. Suarez. 2016. Non-Esterified Fatty Acids Profiling in Rheumatoid Arthritis: Associations with Clinical Features and Th1 Response. PLoS ONE 11: e0159573.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Huang, S., J.M. Rutkowsky, R.G. Snodgrass, K.D. Ono-Moore, D.A. Schneider, J.W. Newman, S.H. Adams, and D.H. Hwang. 2012. Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. Journal of Lipid Research 53: 2002–2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lee, J.Y., K.H. Sohn, S.H. Rhee, and D. Hwang. 2001. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. Journal of Biological Chemistry 276: 16683–16689.

    Article  CAS  PubMed  Google Scholar 

  18. Kochumon, S., H. Arefanian, R. Azim, S. Shenouda, T. Jacob, N. Abu Khalaf, F. Al-Rashed, A. Hasan, S. Sindhu, F. Al-Mulla, et al. 2020. Stearic acid and TNF-alpha Co-Operatively potentiate MIP-1alpha production in monocytic cells via MyD88 independent TLR4/TBK/IRF3 signaling pathway. Biomedicines 8: 403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kawabata, K., N. Baba, T. Sakano, Y. Hamano, S. Taira, A. Tamura, S. Baba, M. Natsume, T. Ishii, S. Murakami, et al. 2018. Functional properties of anti-inflammatory substances from quercetin-treated Bifidobacterium adolescentis. Bioscience, Biotechnology, and Biochemistry 82: 689–697.

    Article  CAS  PubMed  Google Scholar 

  20. Nishitani, Y., S. Okazaki, K. Imabayashi, R. Katada, K. Umetani, H. Yajima, and H. Matsumoto. 2007. Saturated and monounsaturated fatty acids increase interleukin-10 production in rat hepatocytes. Nihon Arukoru Yakubutsu Igakkai Zasshi 42: 32–35.

    CAS  PubMed  Google Scholar 

  21. Pan, P.H., S.Y. Lin, Y.C. Ou, W.Y. Chen, Y.H. Chuang, Y.J. Yen, S.L. Liao, S.L. Raung, and C.J. Chen. 2010. Stearic acid attenuates cholestasis-induced liver injury. Biochemical and Biophysical Research Communications 391: 1537–1542.

    Article  CAS  PubMed  Google Scholar 

  22. Fischman, D., A. Valluri, V.S. Gorrepati, M.E. Murphy, I. Peters, and P. Cheriyath. 2010. Bilirubin as a Protective Factor for Rheumatoid Arthritis: An NHANES Study of 2003–2006 Data. Journal of Clinical Medical Research 2: 256–260.

    CAS  Google Scholar 

  23. Secchi, A.G., I. Fregona, and F. D’Ermo. 1979. Lysophosphatidyl choline in the aqueous humour during ocular inflammation. British Journal of Ophthalmology 63: 768–770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rikitake, Y., K. Hirata, S. Kawashima, S. Takeuchi, Y. Shimokawa, Y. Kojima, N. Inoue, and M. Yokoyama. 2001. Signaling mechanism underlying COX-2 induction by lysophosphatidylcholine. Biochemical and Biophysical Research Communications 281: 1291–1297.

    Article  CAS  PubMed  Google Scholar 

  25. Olofsson, K.E., L. Andersson, J. Nilsson, and H. Bjorkbacka. 2008. Nanomolar concentrations of lysophosphatidylcholine recruit monocytes and induce pro-inflammatory cytokine production in macrophages. Biochemical and Biophysical Research Communications 370: 348–352.

    Article  CAS  PubMed  Google Scholar 

  26. Ryborg, A.K., B. Deleuran, K. Thestrup-Pedersen, and K. Kragballe. 1994. Lysophosphatidylcholine: A chemoattractant to human T lymphocytes. Archives of Dermatological Research 286: 462–465.

    Article  CAS  PubMed  Google Scholar 

  27. Hung, N.D., D.E. Sok, and M.R. Kim. 2012. Prevention of 1-palmitoyl lysophosphatidylcholine-induced inflammation by polyunsaturated acyl lysophosphatidylcholine. Inflammation Research 61: 473–483.

    Article  CAS  PubMed  Google Scholar 

  28. Miyabe, Y., C. Miyabe, Y. Iwai, A. Takayasu, S. Fukuda, W. Yokoyama, J. Nagai, M. Jona, Y. Tokuhara, R. Ohkawa, et al. 2013. Necessity of lysophosphatidic acid receptor 1 for development of arthritis. Arthritis and Rheumatism 65: 2037–2047.

    Article  CAS  PubMed  Google Scholar 

  29. Santos, A.N., D. Riemann, A.N. Santos, A. Kehlen, K. Thiele, and J. Langner. 1996. Treatment of fibroblast-like synoviocytes with IFN-gamma results in the down-regulation of autotaxin mRNA. Biochemical and Biophysical Research Communications 229: 419–424.

    Article  CAS  PubMed  Google Scholar 

  30. Maekawa, K., K. Okemoto, M. Ishikawa, R. Tanaka, Y. Kumagai, and Y. Saito. 2017. Plasma Lipidomics of Healthy Japanese Adults Reveals Gender- and Age-Related Differences. Journal of Pharmaceutical Sciences 106: 2914–2918.

    Article  CAS  PubMed  Google Scholar 

  31. Fu, J., B.V. Cuppen, P.M. Welsing, H. van Wietmarschen, A.C. Harms, R. Barger, S. Koval, R.D. Fitsch-Stork, J.W. Bijlsma, T. Hankemeier, et al. 2016. Differences between serum polar lipid profiles of male and female rheumatoid arthritis patients in response to glucocorticoid treatment. Inflammopharmacology 24: 397–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Maranini, B., A. Bortoluzzi, E. Silvagni, and M. Govoni. 2022. Focus on Sex and Gender: What We Need to Know in the Management of Rheumatoid Arthritis. Journal of Personalized Medicine 12: 499.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported in part by a Research Promotion Grant from Toho University Graduate School of Medicine (No. 17–01, 20–01); the Program for the Strategic Research Foundation for Private Universities (S1411015) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; and the Private University Research Branding Project from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, Japan

    Shotaro Masuoka, Junko Nishio, Soichi Yamada, Kaichi Kaneko, Makoto Kaburaki, Nahoko Tanaka, Hiroshi Sato, Sei Muraoka, Mai Kawazoe, Satoshi Mizutani, Karin Furukawa, Shinichi Kawai & Toshihiro Nanki

  2. Department of Immunopathology and Immunoregulation, Toho University School of Medicine, Tokyo, Japan

    Junko Nishio

  3. Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Kanagawa, Japan

    Kosuke Saito & Yoshiro Saito

  4. Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Kawasaki, Kanagawa, Japan

    Akiko Ishii-Watabe

  5. Department of Inflammation and Pain Control Research, Toho University School of Medicine, Tokyo, Japan

    Shinichi Kawai

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  1. Shotaro Masuoka
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Contributions

SMasuoka, SY, AI, SK, YS, and TN contributed to the design of the study. All authors contributed to material collection, material preparation, and data collection or analysis. SMasuoka and TN wrote the draft of the manuscript. All authors reviewed the manuscript and approved the final draft.

Corresponding author

Correspondence to Toshihiro Nanki.

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Ethical Approval

The study protocol was approved by the Ethics Committees of the Faculty of Medicine, Toho University (approval numbers: A22060_A19020_A17059_A16030 and A21014_A18084_27060) and National Institute of Health Sciences (approval numbers: 271, 271–2, 271–3). All participants provided their written informed consent for this study.

Competing Interests

JN received research funding from Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim Co., Ltd., Nippon Kayaku Co., Ltd., Ayumi Pharmaceutical Corp., Abbvie GK, Abbott Japan LLC, and GlaxoSmithKline plc. KK has received research grants and/or speaking fees from AbbVie GK, Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co. Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corp., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd. HS has received speaking fees and/or teaching fees from Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Ltd., Asahi Kasei Pharma Corp., and Taisho Pharmaceutical Co., Ltd. SMuraoka has received consultant fee from Asahi Kasei Pharma Corp., and speaker’s bureau from Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Asahi Kasei Pharma Corp. and Astellas Pharma Inc. MK has received speaking fees from Ayumi Pharmaceutical Corp., Asahi Kasei Pharma Corp., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Gilead Sciences Inc, GlaxoSmithKline K.K., Mitsubishi-Tanabe Pharma Corp., Nippon Boehringer Ingelheim Co., Ltd. and Taisho Pharmaceutical Co., Ltd. SMizutani received lectures fees from Janssen Pharmaceutical K.K., Bristol-Myers Squibb Co., Chugai Pharmaceutical Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Novartis Pharma K.K., Eli Lilly Japan K.K., Asahikasei Pharma Corp., Taisho Pharma Co., Ltd., and Ono Pharmaceutical Co., and speakers fees from Chugai Pharmaceutical Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Novartis Pharma K.K., Asahikasei Pharma Corp. and Taisho Pharma Co., Ltd. SK has received research grants and/or speaking fees from AbbVie GK, Astellas Pharma Inc., Ayumi Pharmaceutical Corp., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co. Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corp., Nippon Zoki Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd. TN received grant/research support from Chugai Pharmaceutical Co., Ltd, Eisai Co., Ltd., Eli Lilly Japan K.K., Bristol Myers Squibb Co., Ono Pharmaceutical Co., Ltd., Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Corp., Ayumi Pharmaceutical Corp, Nippon Kayaku Co., Ltd., AbbVie GK, Sanofi K.K., Teijin Pharma Ltd., Taisho Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., UCB Japan Co., Ltd., Pfizer Japan Inc. and Takeda Pharmaceutical Co., Ltd., consultant fees from UCB Japan Co., Ltd., Eisai Co., Ltd. and Chugai Pharmaceutical Co., Ltd., and speakers fees from Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Astellas Pharma Inc., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Asahikasei Pharma Corp., Eli Lilly Japan K.K., Mylan N.V., AbbVie GK, Takeda Pharmaceutical Co., Ltd., Ayumi Pharmaceutical Corp., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corp., UCB Japan Co. Ltd., Nippon Kayaku Co., Ltd., Sanofi K.K., Teijin Pharma Ltd., Gilead Sciences, Inc. and Taisho Pharmaceutical Co., Ltd. The remaining authors declare that they have no conflicts of interest.

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Masuoka, S., Nishio, J., Yamada, S. et al. Relationship Between the Lipidome Profile and Disease Activity in Patients with Rheumatoid Arthritis. Inflammation (2024). https://doi.org/10.1007/s10753-024-01986-8

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